University of Alabama at Birmingham

About: University of Alabama at Birmingham is a education organization based out in Birmingham, Alabama, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 38523 authors who have published 86775 publications receiving 3930642 citations. The organization is also known as: UAB & The University of Alabama at Birmingham.

Colorectal Tumors Responding to 5-Fluorouracil Have Low Gene Expression Levels of Dihydropyrimidine Dehydrogenase, Thymidylate Synthase, and Thymidine Phosphorylase

Abstract: We had previously shown that high gene expressions (mRNA levels) of thymidylate synthase (TS; Leichman et al., J. Clin. Oncol., 15: 3223-3229, 1997) and thymidine phosphorylase (TP; Metzger et al., Clin. Cancer Res., 4: 2371-2376, 1998) in pretreatment tumor biopsies could identify tumors that would be nonresponsive to 5-fluorouracil (5-FU)-based therapy. In this study, we investigated the association between intratumoral gene expression of the pyrimidine catabolism enzyme dihydropyrimidine dehydrogenase (DPD) and the response of colorectal tumors to the same 5-FU-based protocol. DPD expressions were measured by quantitative reverse transcription-PCR in 33 pretreatment biopsies of colorectal tumors from patients who went on to receive treatment with 5-FU and leucovorin (LV). The range of DPD gene expression in those tumors that were nonresponsive to 5-FU was much broader than that of the responding tumors. None of the tumors with basal-level DPD expressions above a DPD:beta-actin ratio of 2.5 x 10(-3) (14 of 33) were responders to 5-FU/LV therapy, whereas those tumors with DPD gene expressions below DPD: beta-actin ratio of 2.5 x 10(-3) had a response rate of 50%. There was no correlation among DPD, TS, and TP expression values in this set of colorectal tumors, which indicated that these gene expressions are independent variables. All of the tumors that responded to 5-FU therapy (11 of 33) had expression values of all three of the genes, TS, TP, and DPD, below their respective nonresponse cutoff values, whereas, in each of the nonresponding tumors, at least one of these gene expressions was high. The patients with low expression of all three of the genes had significantly longer survival than patients with a high value of any one of the gene expressions. The results of this study show that intratumoral gene expression level of DPD is associated with tumor response to 5-FU and that the use of more than one independent determinant of response permits the identification of a high percentage of responding patients.

Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life.

Abstract: A natural history study of pneumococcal infection in 82 infants followed from birth is reported. Longitudinal carriage patterns were determined by serial throat and nasopharyngeal cultures. Seventy-nine of 82 infants carried one or more types during the study period. The first type was acquired by a mean age of six months, and the duration of carriage decreased with successive types carried. Acquisition of new types peaked in winter months, but carriage rates fluctuated throughout the year. Thirty-one pneumococcal infections were documented in 24 infants: 28 episodes of otitis media, two of bacteremia, and one of meningitis. Types causing disease were similar to commonly carried types (6, 14, 19 and 23). However, infection usually occurred within one month of acquisition of a new type and was seldom associated with prolonged carriage. In terms of exposure to new strains, 15% (31 of 196) of acquisitions resulted in disease.

Coherence of gamma-band EEG activity as a basis for associative learning.

Abstract: Different regions of the brain must communicate with each other to provide the basis for the integration of sensory information, sensory-motor coordination and many other functions that are critical for learning, memory, information processing, perception and the behaviour of organisms. Hebb suggested that this is accomplished by the formation of assemblies of cells whose synaptic linkages are strengthened whenever the cells are activated or 'ignited' synchronously. Hebb's seminal concept has intrigued investigators since its formulation, but the technology to demonstrate its existence had been lacking until the past decade. Previous studies have shown that very fast electroencephalographic activity in the gamma band (20-70 Hz) increases during, and may be involved in, the formation of percepts and memory, linguistic processing, and other behavioural and perceptual functions. We show here that increased gamma-band activity is also involved in associative learning. In addition, we find that another measure, gamma-band coherence, increases between regions of the brain that receive the two classes of stimuli involved in an associative-learning procedure in humans. An increase in coherence could fulfil the criteria required for the formation of hebbian cell assemblies, binding together parts of the brain that must communicate with one another in order for associative learning to take place. In this way, coherence may be a signature for this and other types of learning.

miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis

Abstract: Uncontrolled extracellular matrix production by fibroblasts in response to tissue injury contributes to fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), a progressive and ultimately fatal process that currently has no cure. Although dysregulation of miRNAs is known to be involved in a variety of pathophysiologic processes, the role of miRNAs in fibrotic lung diseases is unclear. In this study, we found up-regulation of miR-21 in the lungs of mice with bleomycin-induced fibrosis and also in the lungs of patients with IPF. Increased miR-21 expression was primarily localized to myofibroblasts. Administration of miR-21 antisense probes diminished the severity of experimental lung fibrosis in mice, even when treatment was started 5–7 d after initiation of pulmonary injury. TGF-β1, a central pathological mediator of fibrotic diseases, enhanced miR-21 expression in primary pulmonary fibroblasts. Increasing miR-21 levels promoted, whereas knocking down miR-21 attenuated, the pro-fibrogenic activity of TGF-β1 in fibroblasts. A potential mechanism for the role of miR-21 in fibrosis is through regulating the expression of an inhibitory Smad, Smad7. These experiments demonstrate an important role for miR-21 in fibrotic lung diseases and also suggest a novel approach using miRNA therapeutics in treating clinically refractory fibrotic diseases, such as IPF.